1. Field of the Invention
This invention relates to novel glycoproteins obtained from an extract or a supernatant of culture medium of reticulo-endothelial cells, lymphoblasts, leukemia cells or fibroblasts of warm-blooded animals, processes for their production and therapeutic agents for malignant tumors which contain such glycoproteins singly or in combination as an active ingredient.
2. Description of the Prior Art
There has been known no perfect therapy for tumors, and in spite of the fact that many therapeutic agents for tumors have hitherto been developed by a number of researchers in the world, there have been many attempts to use new therapeutic agents and multi-agent combination treatments in the clinical field.
Therapeutic agents for tumors are roughly classified into two categories, chemotherapeutic agents and immunotherapeutic agents. Chemotherapeutic agents, also known as cytotoxic substances, manifest their effect by nonspecifically suppressing cell growth and hence are toxic not only to tumor cells but also to normal cells, and show serious adverse reactions such as leukocytopenia, acyesis, alopecia, teratism, malignant neoplasms, etc.; consequently, there is a strict restriction on the dosage. On the other hand, since the immunotherapeutic agents manifest their therapeutic effect by indirectly inhibiting tumor growth through acting upon the biophylactic functions and not by directly inhibiting the growth of the tumor cells, there is far less danger for serious adverse reactions as compared with chemotherapeutic agents. However, tumor patients do not often retain enough biophylactic functions and therefore the therapeutic effect of immunotherapeutic agents is not always satisfactory as compared with that of chemotherapeutic agents.
The present inventors conceived that the reticulo-endothelial cells which play an important role in biophylactic functions produce a substance which is effective for treating tumors, and have been searching for this substance.
Several factors considered as promising therapeutic agents for tumors, e.g. Lymphotoxin, Tumor Necrosis Factor, Interferon, etc., have been obtained from reticulo-endothelial cells, as reported by Granger, G. A. et al., Cellular Immunology, Vol. 38, 338-402 (1978); Carswell, E. A. et al., Proc. Natl. Acad. Sci. U.S.A., Vol. 72, 3666-33670 (1975); and Issacs, A. et al., Proc. Roy. Soc. Ser. B., Vol. 147, 268 (1975), respectively. Further, the present inventors have recently discovered a simple method for isolating a large amount of Carcino-Breaking Factor (hereinafter referred to as CBF) as a mixture which contains the aforesaid Lymphotoxin, Tumor Necrosis Factor, etc. from a culture of lymphoblasts grown in hamsters whose immune response had been suppressed, and have reported that this CBF is effective against experimental tumors transplanted to an animal (The Yomiuri, morning issue, Nov. 22, 1981).
During the course of the research on CBF, the present inventors have discovered that glycoproteins which differ from the aforesaid cytotoxic factors such as Lymphotoxin, Tumor Necrosis Factor, CBF, etc. are present in an extract or a supernatant of culture medium of reticulo-endothelial cells, lymphoblasts, leukemia cells or fibroblasts of warm-blooded animals, and are characterized by a very strong and selective cytotoxic effect against tumor cells. The present inventors have also established several processes for producing such glycoproteins without difficulties.